Combination Treatment of Stereotactic Body Radiation Therapy and Immature Dendritic Cell Vaccination for Augmentation of Local and Systemic Effects
- Author:
Chul Won CHOI
1
;
Min Ho JEONG
;
You Soo PARK
;
Cheol Hun SON
;
Hong Rae LEE
;
Eun Kyoung KOH
Author Information
- Publication Type:Original Article
- Keywords: Stereotactic body radiotherapy; Immunotherapy; Immature dendritic cells; Tumor antigen
- MeSH: Animals; Annexin A5; Cell Line; Colon; Dendritic Cells; Immune System; Immunotherapy; Injections, Intradermal; Leg; Methods; Mice; Phagocytosis; Radiation Dosage; Radiosurgery; Survival Rate; T-Lymphocytes; Vaccination
- From:Cancer Research and Treatment 2019;51(2):464-473
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs). MATERIALS AND METHODS: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system. RESULTS: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group. CONCLUSION: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.
